May/June 2016
11
sequencing will change the management of dementia patients,
affect expectations of their physicians, and further the quest for
treatments,” she says.
With philanthropic support from the Ellison Foundation, Jayadev is
running what is essentially a dress rehearsal of a precision medi-
cine-era dementia clinic. The cast includes an exome sequencing
team at the UW Center for Precision Diagnostics, a neurogeneti-
cist, a genetic counselor, and a cohort of people who have early
stage dementia or a family history of dementia but no known
genetic mutation.
The study participants, who have agreed to learn the results of
their exome sequencing, may finally get an answer to their ques-
tion: “Why me?” Others will learn that they carry a rare genetic
variant, but that it’s not certain how much it raises their risk of
developing dementia in the next decade. Brad Rolf, a genetic
counselor at UW, will evaluate what works and what doesn’t work
in the conversations, whether people get what they expect, and
how that translates to satisfaction.
From Rolf’s perspective, there’s far-reaching value in creating a
model for exome-based genetic counseling in neurology. “Many
neurologists have taken a special interest in genetics because
so many of the conditions they see have a genetic basis,” he
says. “In the future, more providers who don’t have an expertise
in genetics will be ordering exome-sequencing tests. We hope
that a summary of our experience can help provide guidance
for genetic counseling in this particular population, especially as
single-gene tests are phased out and exome sequencing becomes
a first-line choice.”
On the research side, Jayadev and her team have no small task.
She aims to amass and characterize the different genetic finger-
prints that mark neurodegenerative conditions in patients. The
idea is to group people based on their underlying biochemical
flaw. This risk stratification gives a glimpse at how precision
medicine in Alzheimer’s disease would actually work—guiding
precise diagnoses and selection of presymptomatic participants
for clinical trials of therapeutics that have a chance of success.
Clinical trials are already going full steam ahead. The ADRC serves
as a site of several new trials of new antibodies against Alzheimer’s
pathology, including the A4 Study, DIAN TU, and Biogen’s
EMERGE. These studies are enrolling people with confirmed
amyloid build-up in their brains or individuals at a high genetic
risk. “Therapeutics,” says Jayadev, “will be more effective if given
to the patients in the earliest stages of neurodegeneration.”
As new cognitive, imaging, and genetic biomarkers slowly enter
into clinical application, it becomes possible to imagine a more
hopeful future. In this vision, a person with memory concerns
walks into his family clinic and leaves with a guidebook for next
steps forward instead of more questions. A genetically affected
family receives a preventive medication tailored just for them.
For now, ADRC researchers need to continue improving the
predictive potential of brain scans, enrolling research partici-
pants, and sequencing exomes. And Giuseppe just has to keep
finding those bananas
.
The ADRC is part of the research consortium of the UW Memory and Brain
Wellness Center (MBWC). For news and information about Alzheimer’s,
Parkinson’s, and FTD research, clinical care, and community outreach, visit the
MBWC website at depts.washington.edu/mbwc.
FEATURE
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Exome sequencing is the most practical way to identify the genetic culprits in Alzheimer
disease.
Image credit: National Human Genome Research Institute (NHGRI)
